SPHYNCS: Feasibility of long-term monitoring with Fitbit smartwatches in central disorders of hypersomnolence and extraction of digital biomarkers in narcolepsy.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a multicenter research initiative to identify new biomarkers in central disorders of hypersomnolence (CDH). Whereas narcolepsy type 1 (NT1) is well characterized, other CDH disorders lack precise biomarkers. In SPHYNCS, we utilized Fitbit smartwatches to monitor physical activity, heart rate, and sleep parameters over one year. We examined the feasibility of long-term ambulatory monitoring using the wearable device. We then explored digital biomarkers differentiating patients with NT1 from healthy controls (HC). A total of 115 participants received a Fitbit smartwatch. Using a compliance metric to evaluate the usability of the wearable device, we found an overall compliance rate of 80% over one year. We calculated daily physical activity, heart rate, and sleep parameters from two weeks of greatest compliance to compare NT1 (n=20) and HC (n=9) subjects. Compared to controls, NT1 patients demonstrated findings consistent with increased sleep fragmentation, including significantly greater wake-after-sleep onset (p=0.007) and awakening index (p=0.025), as well as standard deviation of time in bed (p=0.044). Moreover, NT1 patients exhibited a significantly shorter REM latency (p=0.019), and sleep latency (p=0.001), as well as a lower peak heart rate (p=0.008), heart rate standard deviation (p=0.039) and high-intensity activity (p=0.009) compared to HC. This ongoing study demonstrates the feasibility of long-term monitoring with wearable technology in patients with CDH and potentially identifies a digital biomarker profile for NT1. While further validation is needed in larger datasets, these data suggest that long-term wearable technology may play a future role in diagnosing and managing narcolepsy.

Potential immunological triggers for narcolepsy and idiopathic hypersomnia: Real-world insights on infections and influenza vaccinations.

OBJECTIVE: It is hypothesized that narcolepsy type 1 (NT1) develops in genetically susceptible people who encounter environmental triggers leading to immune-mediated hypocretin-1 deficiency. The pathophysiologies of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) remain unknown. The main aim of this study was to collect all reported immunological events before onset of a central disorder of hypersomnolence. METHODS: Medical records of 290 people with NT1, and 115 with NT2 or IH were retrospectively reviewed to extract infection and influenza vaccination history. Prevalence, distribution of immunological events, and time until hypersomnolence onset were compared between NT1 and the combined group of NT2 and IH. RESULTS: Immunological events were frequently reported before hypersomnolence disorder onset across groups. Flu and H1N1 influenza vaccination were more common in NT1, and Epstein-Barr virus and other respiratory and non-respiratory infections in NT2 and IH. Distributions of events were comparable between NT2 and IH. Rapid symptom onset within one month of infection was frequent across groups, especially after flu infection in NT1. Hypersomnolence disorder progression after an immunological event was reported in ten individuals. CONCLUSIONS: Our findings suggest a variety of immunological triggers potentially related to NT1, including H1N1 influenza infection or vaccination, infection with other flu types, and other respiratory and non-respiratory infections. Frequent reports of immunological events (other than those reported in NT1) immediately prior to the development of NT2 and IH support the specificity of triggers for NT1, and open important new research avenues into possible underlying immunological mechanisms in NT2 and IH.

Cumulative brain desaturation: Time to consider brain derived parameters to measure daytime sleepiness in obstructive sleep apnea.

OBJECTIVE: /Background: The change in cerebral hemodynamics induced by sleep apneas and hypopneas may contribute to the daytime sleepiness in patients with obstructive sleep apnea (OSA). However, previous studies failed to discovery their relationship. We propose and test a new parameter, the cumulative brain oxygen desaturation, which may contribute to OSA patient's daytime sleepiness. PATIENTS/METHODS: 22 patients with severe OSA (apnea-hypopnea index (AHI) at diagnosis [mean ± standard deviation, std.]: 52.1 ± 21.6/h, median: 45.1/h, interquartile range: 34.4-60.2/h) were monitored by polysomnography during routine continuous positive airway pressure titration. The reductions of brain tissue oxygen saturation (StO2) in all respiratory events at baseline sleep were measured by frequency-domain near-infrared spectroscopy (NIRS). The cumulative brain desaturation was calculated as AHI times the mean StO2 desaturation (i.e., AHI×ΔStO2‾). Similarly, cumulative peripheral desaturation was also calculated, i.e., AHI×ΔSpO2‾ where ΔSpO2‾ was the mean reduction of peripheral arterial oxygen saturation (SpO2). The correlations between Epworth sleepiness scale (ESS) and AHI, ΔStO2‾, AHI×ΔStO2‾, and AHI×ΔSpO2‾ were tested, respectively. Linear regression was applied to predict ESS using AHI×ΔStO2‾ and AHI×ΔSpO2‾, with age and BMI as covariates. RESULTS: ESS significantly correlates to the cumulative brain desaturation (Pearson's correlation coefficient: 0.68, p = 0.00056), not the other parameters. Regression analysis only finds significant association between ESS and the cumulative cerebral desaturation (p = 0.00195) but not the cumulative peripheral desaturation (p = 0.71). CONCLUSIONS: The cumulative brain oxygen desaturation, which comprehensively combines total sleep time, the frequency of apnea and hypopnea events, and the severity of cerebral oxygen desaturation, is a new indicator for daytime sleepiness in severe OSA.

Impact of social support and religiosity/spirituality on recovery from acute cardiac events and heart surgery in a Swiss study.

OBJECTIVE: The aim of this study was to evaluate the impact of social support and religiosity/spirituality (R/S) on the recovery from an acute cardiac event or cardiac surgery during cardiac rehabilitation (CR). METHODS: The study has a prospective design. A convenience sample of 159 patients participating in a CR program were enrolled. Religiosity/spirituality, social support, anxiety, depression, health related quality of life (QoL) and exercise capacity (6-min walk test, cycle ergometer test) were assessed. RESULTS: Social support was significantly associated with less anxiety (P < .01), less depression (P < .01), and better QoL (P < .05) on admission. After adjustment for age, gender, education level, and morbidity, social support remained significantly associated with less depression (P < .001). Religiosity/spirituality was significantly associated with less depression (P < .05), better QoL (P < .05), and better exercise capacity (P < .05) at admission. After adjustment for covariates, however, significance was lost. There were no significant associations of social support or R/S with the course of CR measured by change in QoL or exercise capacity. CONCLUSION: Social support may be a protective factor against depression in the recovery from cardiac events or surgery. Neither social support nor R/S had a significant impact on the course of the 3-week CR program.

The Comparison of Early Hemodynamic Response to Single-Pulse Transcranial Magnetic Stimulation following Inhibitory or Excitatory Theta Burst Stimulation on Motor Cortex.

We present a new study design aiming to enhance the understanding of the mechanism by which continuous theta burst stimulation (cTBS) or intermittent theta burst stimulation (iTBS) paradigms elicit cortical modulation. Using near-infrared spectroscopy (NIRS), we compared the cortical hemodynamics of the previously inhibited (after cTBS) or excited (after iTBS) left primary motor cortex (M1) as elicited by single-pulse TMS (spTMS) in a cross-over design. Mean relative changes in hemodynamics within 6 s of the stimulus were compared using a two-sample t-test (p < 0.05) and linear mixed model between real and sham stimuli and between stimuli after cTBS and iTBS. Only spTMS after cTBS resulted in a significant increase (p = 0.04) in blood volume (BV) compared to baseline. There were no significant changes in other hemodynamic parameters (oxygenated/deoxygenated hemoglobin). spTMS after cTBS induced a larger increase in BV than spTMS after iTBS (p = 0.021) and sham stimulus after cTBS (p = 0.009). BV showed no significant difference between real and sham stimuli after iTBS (p = 0.37). The greater hemodynamic changes suggest increased vasomotor reactivity after cTBS compared to iTBS. In addition, cTBS could decrease lateral inhibition, allowing activation of surrounding areas after cTBS.

Narcolepsy type 1 and Sydenham chorea - Report of 3 cases and review of the literature.

OBJECTIVES/BACKGROUND: Narcolepsy type 1 (NT1) is an immune-mediated disorder characterized by excessive daytime sleepiness, cataplexy, low levels of hypocretin-1 in the cerebrospinal fluid, and a strong association with the HLA DQB1*06:02 allele. There is evidence for streptococcal infections as one pathogenic factor that may lead to NT1 as part of a multifactorial pathogenesis. Elevated titers of Antistreptolysin-O antibodies and increased inflammatory activity in response to streptococci antigens have been described in patients with NT1. Sydenham chorea (SC) results from a post-streptococcal autoimmune process targeting basal ganglia neurons. Despite this common trigger, SC has been interpreted as a misdiagnosis in a few described cases of patients who were first diagnosed with SC and later with NT1. Our goal was to analyze the association between SC and NT1. PATIENTS/METHODS: We reviewed the literature and report three patients from three European sleep centers who were diagnosed with both SC and NT1 within a few months. RESULTS: We describe the cases of one male (age 10) and two female (age 22 and 10) patients. CONCLUSIONS: We argue that in those cases both diagnoses are justified, unlike reports of previous cases in which SC was considered a misdiagnosis in patients with NT1. It remains, however, unclear if the conditions occur independently or if there is an overlap disorder- an SC-like subtype of narcolepsy with a particular sequence of symptoms. Further studies need to clarify the causality of the relationship and the pathophysiology of the reported rare association.

Idling for Decades: A European Study on Risk Factors Associated with the Delay Before a Narcolepsy Diagnosis.

Purpose: Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy as pathognomonic symptom. Shortening the NT1 diagnostic delay is the key to reduce disease burden and related low quality of life. Here we investigated the changes of diagnostic delay over the diagnostic years (1990-2018) and the factors associated with the delay in Europe. Patients and Methods: We analyzed 580 NT1 patients (male: 325, female: 255) from 12 European countries using the European Narcolepsy Network database. We combined machine learning and linear mixed-effect regression to identify factors associated with the delay. Results: The mean age at EDS onset and diagnosis of our patients was 20.9±11.8 (mean ± standard deviation) and 30.5±14.9 years old, respectively. Their mean and median diagnostic delay was 9.7±11.5 and 5.3 (interquartile range: 1.7-13.2 years) years, respectively. We did not find significant differences in the diagnostic delay over years in either the whole dataset or in individual countries, although the delay showed significant differences in various countries. The number of patients with short (≤2-year) and long (≥13-year) diagnostic delay equally increased over decades, suggesting that subgroups of NT1 patients with variable disease progression may co-exist. Younger age at cataplexy onset, longer interval between EDS and cataplexy onsets, lower cataplexy frequency, shorter duration of irresistible daytime sleep, lower daytime REM sleep propensity, and being female are associated with longer diagnostic delay. Conclusion: Our findings contrast the results of previous studies reporting shorter delay over time which is confounded by calendar year, because they characterized the changes in diagnostic delay over the symptom onset year. Our study indicates that new strategies such as increasing media attention/awareness and developing new biomarkers are needed to better detect EDS, cataplexy, and changes of nocturnal sleep in narcolepsy, in order to shorten the diagnostic interval.

Data-Driven Phenotyping of Central Disorders of Hypersomnolence With Unsupervised Clustering.

BACKGROUND AND OBJECTIVES: Recent studies fueled doubts as to whether all currently defined central disorders of hypersomnolence are stable entities, especially narcolepsy type 2 and idiopathic hypersomnia. New reliable biomarkers are needed, and the question arises of whether current diagnostic criteria of hypersomnolence disorders should be reassessed. The main aim of this data-driven observational study was to see whether data-driven algorithms would segregate narcolepsy type 1 and identify more reliable subgrouping of individuals without cataplexy with new clinical biomarkers. METHODS: We used agglomerative hierarchical clustering, an unsupervised machine learning algorithm, to identify distinct hypersomnolence clusters in the large-scale European Narcolepsy Network database. We included 97 variables, covering all aspects of central hypersomnolence disorders such as symptoms, demographics, objective and subjective sleep measures, and laboratory biomarkers. We specifically focused on subgrouping of patients without cataplexy. The number of clusters was chosen to be the minimal number for which patients without cataplexy were put in distinct groups. RESULTS: We included 1,078 unmedicated adolescents and adults. Seven clusters were identified, of which 4 clusters included predominantly individuals with cataplexy. The 2 most distinct clusters consisted of 158 and 157 patients, were dominated by those without cataplexy, and among other variables, significantly differed in presence of sleep drunkenness, subjective difficulty awakening, and weekend-week sleep length difference. Patients formally diagnosed as having narcolepsy type 2 and idiopathic hypersomnia were evenly mixed in these 2 clusters. DISCUSSION: Using a data-driven approach in the largest study on central disorders of hypersomnolence to date, our study identified distinct patient subgroups within the central disorders of hypersomnolence population. Our results contest inclusion of sleep-onset REM periods in diagnostic criteria for people without cataplexy and provide promising new variables for reliable diagnostic categories that better resemble different patient phenotypes. Cluster-guided classification will result in a more solid hypersomnolence classification system that is less vulnerable to instability of single features.

Predictors of changes in cerebral perfusion and oxygenation during obstructive sleep apnea.

Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder. Severe OSAS defined as apnea-hypopnea index (AHI) ≥ 30/h is a risk factor for developing cerebro-cardiovascular diseases. The mechanisms of how repetitive sleep apneas/hypopneas damage cerebral hemodynamics are still not well understood. In this study, changes in blood volume (BV) and oxygen saturation (StO2) in the left forehead of 29 newly diagnosed severe OSAS patients were measured by frequency-domain near-infrared spectroscopy during an incremental continuous positive airway pressure (CPAP) titration protocol together with polysomnography. The coefficients of variation of BV (CV-BV) and the decreases of StO2 (de-StO2) of more than 2000 respiratory events were predicted using linear mixed-effect models, respectively. We found that longer events and apneas rather than hypopneas induce larger changes in CV-BV and stronger cerebral desaturation. Respiratory events occurring during higher baseline StO2 before their onsets, during rapid-eye-movement sleep and those associated with higher heart rate induce smaller changes in CV-BV and de-StO2. The stepwise increased CPAP pressures can attenuate these changes. These results suggest that in severe OSAS the length and the type of respiratory event rather than widely used AHI may be better parameters to indicate the severity of cerebral hemodynamic changes.

Effectiveness of Pulmonary Rehabilitation in Severe and Critically Ill COVID-19 Patients: A Controlled Study.

BACKGROUND: Severe and critically ill COVID-19 patients frequently need pulmonary rehabilitation (PR) after hospitalization. However, little is known about the effectiveness of PR in COVID-19 patients. METHODS: We compared the performances in the six-min walk test (6MWT), chronic respiratory questionnaire (CRQ), and Functional Independence Measure (FIM) from inpatient PR between 51 COVID-19 patients and 51 other patients with common pneumonia. We used multivariate linear regression controlled for baseline values at entrance, age, sex, and cumulative illness rating scale. The odds ratios (ORs) of non-improvement/improvement in 6MWT (>30-m) and CRQ (>10-point) at discharge were compared between the two groups (Fisher's exact test). RESULTS: The two groups had similar improvements in 6MWT and CRQ, but the COVID-19 group achieved a 4-point higher FIM (p-value = 0.004). The OR of non-improvement/improvement in 6MWT was 0.30 (p-value = 0.13) between COVID-19 and controls; however, the odds of non-improvement in CRQ tended to be 3.02 times higher (p-value = 0.075) in COVID-19 patients. Severe and critical COVID-19 patients had similar rehabilitation outcomes. CONCLUSIONS: Inpatient PR can effectively improve physical functions and life quality in COVID-19 patients, irrespective of disease severity. Whether the relatively low gains in CRQ is an indicator of chronic disease development in COVID-19 patients needs further studies.

The Challenges and Pitfalls of Detecting Sleep Hypopnea Using a Wearable Optical Sensor: Comparative Study.

BACKGROUND: Obstructive sleep apnea (OSA) is the most prevalent respiratory sleep disorder occurring in 9% to 38% of the general population. About 90% of patients with suspected OSA remain undiagnosed due to the lack of sleep laboratories or specialists and the high cost of gold-standard in-lab polysomnography diagnosis, leading to a decreased quality of life and increased health care burden in cardio- and cerebrovascular diseases. Wearable sleep trackers like smartwatches and armbands are booming, creating a hope for cost-efficient at-home OSA diagnosis and assessment of treatment (eg, continuous positive airway pressure [CPAP] therapy) effectiveness. However, such wearables are currently still not available and cannot be used to detect sleep hypopnea. Sleep hypopnea is defined by ≥30% drop in breathing and an at least 3% drop in peripheral capillary oxygen saturation (Spo2) measured at the fingertip. Whether the conventional measures of oxygen desaturation (OD) at the fingertip and at the arm or wrist are identical is essentially unknown. OBJECTIVE: We aimed to compare event-by-event arm OD (arm_OD) with fingertip OD (finger_OD) in sleep hypopneas during both naïve sleep and CPAP therapy. METHODS: Thirty patients with OSA underwent an incremental, stepwise CPAP titration protocol during all-night in-lab video-polysomnography monitoring (ie, 1-h baseline sleep without CPAP followed by stepwise increments of 1 cmH2O pressure per hour starting from 5 to 8 cmH2O depending on the individual). Arm_OD of the left biceps muscle and finger_OD of the left index fingertip in sleep hypopneas were simultaneously measured by frequency-domain near-infrared spectroscopy and video-polysomnography photoplethysmography, respectively. Bland-Altman plots were used to illustrate the agreements between arm_OD and finger_OD during baseline sleep and under CPAP. We used t tests to determine whether these measurements significantly differed. RESULTS: In total, 534 obstructive apneas and 2185 hypopneas were recorded. Of the 2185 hypopneas, 668 (30.57%) were collected during baseline sleep and 1517 (69.43%), during CPAP sleep. The mean difference between finger_OD and arm_OD was 2.86% (95% CI 2.67%-3.06%, t667=28.28; P<.001; 95% limits of agreement [LoA] -2.27%, 8.00%) during baseline sleep and 1.83% (95% CI 1.72%-1.94%, t1516=31.99; P<.001; 95% LoA -2.54%, 6.19%) during CPAP. Using the standard criterion of 3% saturation drop, arm_OD only recognized 16.32% (109/668) and 14.90% (226/1517) of hypopneas at baseline and during CPAP, respectively. CONCLUSIONS: arm_OD is 2% to 3% lower than standard finger_OD in sleep hypopnea, probably because the measured arm_OD originates physiologically from arterioles, venules, and capillaries; thus, the venous blood adversely affects its value. Our findings demonstrate that the standard criterion of ≥3% OD drop at the arm or wrist is not suitable to define hypopnea because it could provide large false-negative results in diagnosing OSA and assessing CPAP treatment effectiveness.

European guideline and expert statements on the management of narcolepsy in adults and children.

BACKGROUND AND PURPOSE: Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children. METHODS: The European Academy of Neurology (EAN), European Sleep Research Society (ESRS), and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach. RESULTS: A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness (EDS) in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong); methylphenidate, amphetamine derivatives (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) EDS in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivatives (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions. CONCLUSION: The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.

European guideline and expert statements on the management of narcolepsy in adults and children.

BACKGROUND AND AIM: Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children. METHODS: The European Academy of Neurology (EAN), European Sleep Research Society (ESRS) and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach. RESULTS: A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong), methylphenidate, amphetamine derivates (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) excessive daytime sleepiness in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivates (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions. CONCLUSION: The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study.

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH.

Insomnia disorder: clinical and research challenges for the 21st century.

BACKGROUND AND PURPOSE: Insomnia is a common and debilitating disorder that is frequently associated with important consequences for physical health and well-being. METHODS: An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years, discussed the current challenges in the field of insomnia and identified future priorities. RESULTS: The association of trajectories of insomnia with subsequent quality of life, health and mortality should be investigated in large populations. Prospective health economics studies by separating the costs driven specifically by insomnia and costs attributable to its long-term effects are needed. Ignoring the heterogeneity of insomnia patients leads to inadequate diagnosis and inefficient treatment. Individualized interventions should be promoted. More data are needed on both the impact of sleep on overnight effects, such as emotion regulation, and the potential compensatory effort to counteract diurnal impairments. Another gap is the definition of neurocognitive deficits in insomnia patients compared to normal subjects after chronic sleep loss. There are also a number of key gaps related to insomnia treatment. Expert guidelines indicate cognitive-behavioural therapy for insomnia as first-line treatment. They neglect, however, the reality of major healthcare providers. The role of combined therapy, cognitive-behavioural therapy for insomnia plus pharmacological treatment, should be evaluated more extensively. CONCLUSION: Whilst insomnia disorder might affect large proportions of the population, there are a number of significant gaps in the epidemiological/clinical/research studies carried out to date. In particular, the identification of different insomnia phenotypes could allow more cost-effective and efficient therapies.

Quantitative Changes in Muscular and Capillary Oxygen Desaturation Measured by Optical Sensors during Continuous Positive Airway Pressure Titration for Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a common sleep disorder, and continuous positive airway pressure (CPAP) is the most effective treatment. Poor adherence is one of the major challenges in CPAP therapy. The recent boom of wearable optical sensors measuring oxygen saturation makes at-home multiple-night CPAP titrations possible, which may essentially improve the adherence of CPAP therapy by optimizing its pressure in a real-life setting economically. We tested whether the oxygen desaturations (ODs) measured in the arm muscle (arm_OD) by gold-standard frequency-domain multi-distance near-infrared spectroscopy (FDMD-NIRS) change quantitatively with titrated CPAP pressures in OSA patients together with polysomnography. We found that the arm_OD (2.08 ± 1.23%, mean ± standard deviation) was significantly smaller (p-value < 0.0001) than the fingertip OD (finger_OD) (4.46 ± 2.37%) measured by a polysomnography pulse oximeter. Linear mixed-effects models suggested that CPAP pressure was a significant predictor for finger_OD but not for arm_OD. Since FDMD-NIRS measures a mixture of arterial and venous OD, whereas a fingertip pulse oximeter measures arterial OD, our results of no association between arm_OD and finger_OD indicate that the arm_OD mainly represented venous desaturation. Arm_OD measured by optical sensors used for wearables may not be a suitable indicator of the CPAP titration effectiveness.

New 2013 incidence peak in childhood narcolepsy: more than vaccination?

Increased incidence rates of narcolepsy type-1 (NT1) have been reported worldwide after the 2009-2010 H1N1 influenza pandemic (pH1N1). While some European countries found an association between the NT1 incidence increase and the H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus itself to be linked to the increased NT1 incidence. Using robust data-driven modeling approaches, that is, locally estimated scatterplot smoothing methods, we analyzed the number of de novo NT1 cases (n = 508) in the last two decades using the European Narcolepsy Network database. We confirmed the peak of NT1 incidence in 2010, that is, 2.54-fold (95% confidence interval [CI]: [2.11, 3.19]) increase in NT1 onset following 2009-2010 pH1N1. This peak in 2010 was found in both childhood NT1 (2.75-fold increase, 95% CI: [1.95, 4.69]) and adulthood NT1 (2.43-fold increase, 95% CI: [2.05, 2.97]). In addition, we identified a new peak in 2013 that is age-specific for children/adolescents (i.e. 2.09-fold increase, 95% CI: [1.52, 3.32]). Most of these children/adolescents were HLA DQB1*06:02 positive and showed a subacute disease onset consistent with an immune-mediated type of narcolepsy. The new 2013 incidence peak is likely not related to Pandemrix as it was not used after 2010. Our results suggest that the increased NT1 incidence after 2009-2010 pH1N1 is not unique and our study provides an opportunity to develop new hypotheses, for example, considering other (influenza) viruses or epidemiological events to further investigate the pathophysiology of immune-mediated narcolepsy.